Variant 6-37450255-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015050.3(CMTR1):c.449G>A(p.Ser150Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CMTR1
NM_015050.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Variant links:

Genes affected

CMTR1 (HGNC:21077): (cap methyltransferase 1) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap1 mRNA methylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CMTR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042013496).

BS2

High AC in GnomAdExome4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CMTR1	NM_015050.3 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	5/24	ENST00000373451.9	NP_055865.1
CMTR1	XM_047418462.1 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	6/25		XP_047274418.1
CMTR1	XM_047418463.1 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	7/26		XP_047274419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMTR1	ENST00000373451.9 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	5/24	1	NM_015050.3	ENSP00000362550	P1
CMTR1	ENST00000455891.5 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	5/10	2		ENSP00000414233

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251438

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000506

AC:

AN:

1461714

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000672

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.449G>A (p.S150N) alteration is located in exon 5 (coding exon 4) of the CMTR1 gene. This alteration results from a G to A substitution at nucleotide position 449, causing the serine (S) at amino acid position 150 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.028

.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.027

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.12

Sift

Benign

0.26

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0020

B;B

Vest4

0.19

MutPred

0.34

Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);

MVP

0.18

MPC

0.75

ClinPred

0.058

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.17

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over